Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Proteinuria Jonathan Stein, MD MSH AIMGP Seminar Series Objectives Cases Dipstick analysis Mechanisms of proteinuria Transient vs. persistent proteinuria Benign orthostatic proteinuria Non-proliferative causes Proliferative Case study #1 22M, routine annual check up, found to have 2+ proteinuria on dipstick No Pmhx, otherwise healthy What workup is necessary? Case study #2 65F, vague abdominal pain x 2 months, found to have 4+ proteinuria on dipstick Pmhx: blood transfusion in 1985 Hx: weight loss 20 lbs over 6 months What work up is necessary? Proteinuria Normal protein in urine <150 mg/day Approx 30 mg is albumin Rest is secreted by tubules: Tamm Horsfall, IgA, Haptoglobin, transferrin, B2 microglobulin Urine dipstick measures negatively charged proteins only = albumin Proteinuria typically picked up by urine dipstick testing Dipstick: reaction specific for albumin JUG 24 hour urine: measures all protein excreted (albumin and nonalbumin) Limitations of Dipstick False positives: concentrated urine, ph>7.0, hematuria False negatives: dilute urine, predominate protein not albumin Adding sulfasalicylic acid will precipitate non albumin proteins Proteinuria – 3 mechanisms “Leaky” glomerular capillary barrier 1. • • allows albumin (and sometimes globulin) to cross into Bowman’s space this is what occurs in many forms of glomerulonephritis Glomerular barrier tubule • Normally, the larger proteins are excluded at the glomerular barrier • Smaller proteins can pass, but are mostly reabsorbed Leaky Glomerular barrier tubule •Large proteins are able to pass by the abnormal glomerular barrier Proteinuria – 3 mechanisms Malfunctioning tubular reabsorption of smaller proteins 2. • • • • albumin excluded at (normal) glomerular barrier sick tubules unable to reabsorb the normally-filtered smaller proteins “tubular” proteinuria eg., tubulointerstitial nephropathy Tubular Reabsorption Malfunctioning tubule Malfunctioning tubules unable to reabsorb the smaller proteins filtered at the glomerulus Proteinuria – 3 mechanisms 3. “Overflow” proteinuria filtered load of proteins exceeds capacity of tubules to reabsorb it all “filtered load” = plasma concentration X GFR increased plasma concentration: ie: excess light chains increased GFR: pregnancy, fever, hyperglycemia Overflow Glomerular barrier tubule • Filtered load of proteins exceeds the tubular reabsorption rate (similar to glucosuria in hyperglycemia) Approach to Proteinuria History: urinary symptoms, infections, rash, risk factors for HIV and hepatitis Pmhx: Cancer, CHF, HTN, CTD, DM, CTD FHx: Alports, Fabry’s Drugs: NSAIDS, Gold, Heroin Physical exam: vitals, JVP, peripheral edema, ascites, rash, joint swellings Arsenal of Investigations Work up: Dipstick 1+ or greater Urinanalysis (protein, casts) Random urine: alb:creat ratio Overnight supine and daytime upright 24 hour urine for protein Blood work (basic vs. extensive) Renal imaging U/S, CT Biopsy Transient vs. Persistent Proteinuria Transient Fever CHF Post exercise >>>> No further testing required Persistent Proteinuria: Benign Benign orthostatic proteinuria Usually <1-2 g/d Mostly in young, otherwise well Often disappears by adulthood Investigations: Obtain overnight supine and daytime upright urine collection Benign Orthostatic Proteinuria Split urine collection first morning urine is discarded 16 hour ambulatory collection assume recumbent position 2h before start of supine collection overnight 8 hour supine collection total protein and total creatinine in each collection Benign orthostatic proteinuria Results: No blood or casts on urinalysis Renal function and blood pressure normal Confirmation: < 50 mg of protein in the supine collection rest of protein in the upright collection Benign orthostatic proteinuria 3 theories about the pathogenesis exaggeration of the normal response of transient increase in urine protein upon taking the upright posture subtle glomerular abnormalities renal vein compression by aorta or superior mesenteric artery Non-proliferative Causes of Proteinuria: Nephrotic range proteinuria: >3.5 g/d 1. Minimal change: Primary & Secondary (2o = Hodgkin's, NSAIDS, Rifampin) 2. FSGS: Primary & Secondary (2o = HIV, DM, NSAIDS, heroin, chronic pyelonephritis, reflux nephropathy) Non-proliferative: Nephrotic Syndrome 3. Membranous: Primary & Secondary 2o causes = vasculitis – SLE infections – hep B,C, syphilis, malaria, toxoplasmosis others: SBE, cancer, drugs (gold, penicillin, captopril), DM, sarcoid, sickle cell 4. Nodular: DM, amyloid Complications of Nephrotic Syndrome Edema Hypoalbuminemia Hyperlipidemia (Cholesterolemia) Hypercoaguability – loss of AT III, protein S,C IgG deficiency – decreased immunity Diagnostic Work Up CBC, lytes, Ca, Phos Serum creatinine, creatine clearance Fasting blood sugar Serum and urine protein electrophoresis Serology: Hep B, Hep C Antistreptolysin O titer ANA, Rheum factor, C3/C4 HIV, VDRL Abdominal U/S – rule out PCKD CXR Renal Biopsy Rule of Thumb Nephrotic range proteinuria in the elderly, think about: 1) Diabetes 2) Malignancy 3) Multiple myeloma Membranoproliferative Glomerulonephropathy Type I: subendothelial and mesangial deposits on EM that contain C3 and IgG Nephrotic proteinuria, active sediment, low C3, immune complex disease Associated with: chronic infections, systemic disease, malignancy, others (sarcoid, heroin) Type II: Can present as nephritic syndrome Autoimmune disease IgG antibody (nephritic factor) Nephritic Syndrome Definition: Proliferative GN, RBC casts, hematuria, HTN, mild proteinuria, edema Focal proliferative Diffuse proliferative Rapidly progressive (T1, T2, T3) Membranoproliferative Summary Dipstick analysis – uses & limitations 3 mechanisms of proteinuria: glomerular, tubular, overflow Benign orthostatic proteinuria: <2g/d, split urine collection Nephrotic: Min change, FSGS, Membranous, Nodular Membranoproliferative and Nephritic Work up – begins with 24 hour urine for protein and albumin:creatinine References 1. Practice guidelines for Chronic Kidney Disease. 2003. Annals of Internal medicine. Vol. 139 Number 2. 2. Approach to proteinuria. American family physician. 2000. 62: 1333-40 Thank You !